Dr. Charles Schroeder is an Assistant Professor in the Departnnent of Chemical &Biomolecular Engineering at the University of Illinois at Urbana-Champaign. The candidate has been trained in single molecule polymer physics and single molecule biology and biophysics. The candidate's long-term scientific research goals are to study fundamental processes in biological systems and to develop new technologies based on single molecule tools for genomics, disease diagnosis, and biotechnology. The NIH PI Award (K99 phase) has facilitated the candidate's career development by providing training in protein expression and purification, benchtop biochemistry, enzymology, and single molecule fluorescence imaging. Activiation ofthe ROO phase ofthe NIH PI Award will enable the candidate's laboratory to develop a new single molecule-based genomic technology to benefit human health. The University of Illinois provides an excellent infrastructure forthe proposed technology development and has a vibrant single molecule research community. The overarching goal ofthe candidate's research program is to develop novel single molecule technologies for advancement of human health. The specific goal of the current research proposal (ROO phase) is to develop a single molecule technology for conducting genome-wide association studies for complex diseases and for direct determination of large-scale genomic rearrangements (insertions, deletions and inversions) in a low-cost, high-throughput format. Identification of genes associated with common diseases will lead to a major breakthrough in our understanding ofthe causes of human disease and will catalyze a new paradigm for diagnosis of diseases, prediction of drug response, and development of new disease therapies. The goal of this research proposal will be achieved by addressing the following specific aims: 1.) Demonstration of a high-throughput method for analyzing stretched and trapped genomic DNA molecules using a microfluidic device;2.) Development of molecular tags for sequence-specific marker recognition in genomic DNA;3.) Linking of fluorescent probes to these molecular tags;4.) Development of methods for extraction and manipulation of intact genomic DNA from cells in a "lab-on-a-chip" format